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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Nature Genetics, Volume 46, No. 9, Year 2014
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Description
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Nalls, Mike A.
United States, Bethesda
National Institute on Aging Nia
Pankratz, Nathan D.
United States, Minneapolis
University of Minnesota Twin Cities
Lill, Christina M.
Germany, Berlin
Max Planck Institute for Molecular Genetics
Germany, Mainz
Johannes Gutenberg-universität Mainz
Hernandez, Dena G.
United Kingdom, London
Ucl Queen Square Institute of Neurology
United States, Bethesda
National Institute on Aging Nia
United States, St. Louis
Washington University School of Medicine in St. Louis
Saad, Mohamad
United States, Seattle
University of Washington
France, Toulouse
Institut Toulousain Des Maladies Infectieuses et Inflammatoires Infinity
France, Toulouse
Université Toulouse Iii - Paul Sabatier
Kara, Eleanna
United Kingdom, London
University College London
Brás, José Tomas
United Kingdom, London
University College London
Sharma, Manu
Germany, Tubingen
Eberhard Karls Universität Tübingen
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Schulte, Claudia M.S.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Keller, Margaux F.
United States, Bethesda
National Institute on Aging Nia
Arepalli, Sampath K.
United States, Bethesda
National Institute on Aging Nia
Edsall, Connor
United States, Bethesda
National Institute on Aging Nia
Stefánsson, Hreinn
Iceland, Reykjavik
Decode Genetics
Ikram, Mohammad Arfan
Netherlands, Rotterdam
Erasmus Mc
Ioannidis, John P.A.
United States, Palo Alto
Stanford University
Hadjigeorgiou, Georgios M.
Greece, Volos
University of Thessaly
Bis, Joshua C.M.
United States, Seattle
University of Washington
Martinez, Maria M.
France, Toulouse
Institut Toulousain Des Maladies Infectieuses et Inflammatoires Infinity
France, Toulouse
Université Toulouse Iii - Paul Sabatier
Perlmutter, Joel S.
United States, St. Louis
Washington University School of Medicine in St. Louis
United States, St. Louis
Washington University in St. Louis
Marder, Karen
United States, New York
Columbia University Irving Medical Center
Fiske, Brian K.
United States, New York
The Michael J. Fox Foundation for Parkinson‘s Research
Xiromerisiou, Georgia
Greece, Volos
University of Thessaly
Greece, Thessaloniki
Papageorgiou General Hospital
Stefánsson, Kári
Iceland, Reykjavik
Decode Genetics
Hardy, John A.
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
University College London
Heutink, Peter
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Chen, Honglei
United States, Research Triangle Park
National Institute of Environmental Health Sciences Niehs
United States, Bethesda
National Institutes of Health Nih
Wood, Nick William
United Kingdom, London
University College London
Houlden, Henry H.
United Kingdom, London
University College London
Brice, Alexis
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Paris
Inserm
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Scott, William K.
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Gasser, Thomas
Germany, Tubingen
Eberhard Karls Universität Tübingen
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Bertram, Lars
Germany, Berlin
Max Planck Institute for Molecular Genetics
United Kingdom, London
Imperial College London
Foroud, Tatiana M.
United States, Indianapolis
Indiana University School of Medicine
Singleton, Andrew B.
United States, Bethesda
National Institute on Aging Nia
Plagnol, Vincent
United Kingdom, London
University College London
Sheerin, Una Marie
United Kingdom, London
University College London
Simón-Sánchez, Javier
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Lesage, Suzanne
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Sveinbjörnsdóttir, Sigurlaug
Iceland, Reykjavik
Landspitali - the National University Hospital of Iceland
United Kingdom, Chelmsford
Broomfield Hospital
United Kingdom, London
University of London
A Barker, Roger A.
United Kingdom, Cambridge
Addenbrooke's Hospital
Ben-Shlomo, Yoav
United Kingdom, Bristol
University of Bristol
Berendse, Henk W.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Berg, Daniela
Germany, Tubingen
Eberhard Karls Universität Tübingen
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Bhatia, Kailash P.
United Kingdom, London
Ucl Queen Square Institute of Neurology
de Bie, Rob M.A.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Biffi, Alessandro
United States, Boston
Massachusetts General Hospital
United States, Cambridge
Broad Institute
Bloem, Bastiaan R.
Netherlands, Nijmegen
Radboud University Medical Center
Bochdanovits, Zoltán
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Bonin, Michael
Germany, Tubingen
Eberhard Karls Universität Tübingen
Brás, José Miguel
United Kingdom, London
University College London
Brockmann, Kathrin
Germany, Tubingen
Eberhard Karls Universität Tübingen
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Brooks, Janet A.
United States, Bethesda
National Institute on Aging Nia
Burn, David J.
United Kingdom, Newcastle
Newcastle University
Charlesworth, Gavin
United Kingdom, London
University College London
Chinnery, Patrick Francis
United Kingdom, Newcastle
School of Medical Education
Chong, Sean B.
United States, Bethesda
National Institute on Aging Nia
Clarke, Carl E.
United Kingdom, Birmingham
University of Birmingham
United Kingdom, West Bromwich
Sandwell and West Birmingham Hospitals Nhs Trust
Cookson, Mark R.
United States, Bethesda
National Institute on Aging Nia
Corvol, Jean Christophe
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Inserm
France, Paris
Cnrs Centre National de la Recherche Scientifique
Counsell, Carl E.
United Kingdom, Aberdeen
University of Aberdeen
Damier, Philippe
France, Nantes
Chu de Nantes
Dartigues, Jean François
France, Bordeaux
Université de Bordeaux
Deloukas, Panos
United Kingdom, London
Wellcome Trust
Deuschl, Günther
Germany, Kiel
Christian-albrechts-universität zu Kiel
Dexter, David Trevor
United Kingdom, London
Imperial College London
van Dijk, K. D.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Dillman, Allissa Amanda
United States, Bethesda
National Institute on Aging Nia
Sweden, Stockholm
Karolinska Institutet
Durif, Franck
France, Clermont-ferrand
Hopital Gabriel Montpied
Dúrr, Alexandra
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Edkins, Sarah J.
United Kingdom, London
Wellcome Trust
Foltynie, Thomas
United Kingdom, London
Ucl Queen Square Institute of Neurology
Gibbs, J. Raphael
United States, Bethesda
National Institute on Aging Nia
United Kingdom, London
University College London
Gray, Emma K.
United Kingdom, London
Wellcome Trust
Guerreiro, Rita João
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
University College London
van Hilten, Jacobus Johannes Bob
Netherlands, Leiden
Leids Universitair Medisch Centrum
Hofman, Albert
Netherlands, Rotterdam
Erasmus Mc
Holton, Janice L.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Wurster, Isabel
Germany, Tubingen
Eberhard Karls Universität Tübingen
Hudson, Gavin
United Kingdom, Newcastle
School of Medical Education
Hunt, Sarah E.
United Kingdom, London
Wellcome Trust
Illig, Thomas
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Lambert, Jean Charles
France, Paris
Inserm
France, Lille
Institut Pasteur de Lille
Langford, Cordelia F.
United Kingdom, Cambridge
John Van Geest Centre for Brain Repair
Lees, Andrew John L.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Lichtner, Peter K.
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Limousin, Patricia Dowsey
Unknown Affiliation
Lorenz, Delia
Germany, Kiel
Christian-albrechts-universität zu Kiel
Morris, Huw R.
United Kingdom, Cardiff
Mrc Centre for Neuropsychiatric Genetics and Genomics
Morrison, Karen E.
United Kingdom, Birmingham
University of Birmingham
United Kingdom, Birmingham
University Hospitals Birmingham Nhs Foundation Trust
Pollak, Pierre R.
France, Grenoble
Centre Hospitalier Universitaire de Grenoble
Potter, Simon C.
United Kingdom, London
Wellcome Trust
Revesz, Tamas R.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Riess, Olaf H.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Rivadeneira, Fernando F.
Netherlands, Rotterdam
Erasmus Mc
Rizzu, Patrizia
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Ryten, Mina
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
University College London
Sawcer, Stephen J.
United Kingdom, Cambridge
Addenbrooke's Hospital
Schapira, Anthony HV V.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Sidransky, Ellen
Unknown Affiliation
Smith, Colin Nurse Simon
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, London
Medical Research Council
Spencer, Chris C.A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Bettella, Francesco
Iceland, Reykjavik
Decode Genetics
Stockton, Joanne D.
United Kingdom, Birmingham
University of Birmingham
Strange, Amy
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Talbot, Kevin
United Kingdom, Oxford
John Radcliffe Hospital
Tison, François X.
France, Pessac
Hopital Haut-lévêque C.h.u de Bordeaux
Trabzuni, Daniah
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
University College London
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Traynor, B. J.
United States, Bethesda
National Institute on Aging Nia
Uitterlinden, André G.
Netherlands, Rotterdam
Erasmus Mc
Vidailhet, Marie
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Walker, Robert A.
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, London
Medical Research Council
van de Warrenburg, Bart P.C.
Netherlands, Nijmegen
Radboud University Medical Center
Williams, Nigel M.
United Kingdom, Cardiff
Mrc Centre for Neuropsychiatric Genetics and Genomics
Williams-Gray, Caroline H.
United Kingdom, Cambridge
Addenbrooke's Hospital
Stefánsson, Kari
Iceland, Reykjavik
Decode Genetics
Jankovic, Joseph J.
United States, Houston
Baylor College of Medicine
Hunter, Christine B.
United States, Houston
Baylor College of Medicine
Saunders-Pullman, Rachel J.
United States, Boston
Beth Israel Deaconess Medical Center
Friedman, Joseph Harold
United States, Providence
Brown University
Fernandez, Hubert H.
United States, Providence
Brown University
Gálvez-Jiménez, Néstor A.
United States, Cleveland
Cleveland Clinic Foundation
Marder, Karen S.
United States, New York
Columbia University Irving Medical Center
United States, New York
Gertrude H. Sergievsky Center
Fraser, Jamie L.
United States, New York
Columbia University Irving Medical Center
Harris, Juliette
United States, New York
Columbia University Irving Medical Center
Bertoni, John M.
United States, Omaha
Creighton University
Chouinard, Sylvain
United States, New Orleans
University Medical Center new Orleans
Reich, Stephen G.
United States, Baltimore
Johns Hopkins University
United States, Baltimore
University of Maryland School of Medicine
Uitti, Ryan J.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Elmer, Lawrence W.
Unknown Affiliation
Simuni, Tanya
United States, Evanston
Northwestern University
Fernández-Martínez, Manuel Jesús
United States, Columbus
The Ohio State University
Rajput, Alex H.
Canada, Saskatoon
Royal University Hospital
Manyam, Bala V.
United States, Temple
Scott and White
Lang, Anthony E.
Canada, Toronto
Toronto Western Hospital University of Toronto
Martin, W. R. Wayne
Canada, Edmonton
University of Alberta
Suchowersky, Oksana
Canada, Calgary
University of Calgary
Lyons, Kelly E.
United States, Kansas City
University of Kansas Medical Center
United States, Coral Gables
University of Miami
Pahwa, Rajesh
United States, Kansas City
University of Kansas Medical Center
Kurlan, Roger M.
United States, Rochester
University of Rochester
Hauser, Robert A.
United States, Tampa
University of South Florida, Tampa
Price, Kathy
United States, Tampa
University of South Florida, Tampa
Hayward, Bruce Eliot
United States, Dallas
Ut Southwestern Medical Center
Walker, Francis O.
United States, Winston Salem
Wake Forest University School of Medicine
Racette, Brad A.
United States, St. Louis
Washington University School of Medicine in St. Louis
Swisher, Laura M.
Unknown Affiliation
Tung, Joyce Y.
United States, Mountain View
23andme Inc.
Hinds, David A.
United States, Mountain View
23andme Inc.
Mountain, Joanna L.
United States, Mountain View
23andme Inc.
Klein, Christine
Germany, Lubeck
Universität zu Lübeck
Watts, Raymond G.
United States, Birmingham
The University of Alabama at Birmingham
Guttman, Mark
Canada, Toronto
University of Toronto
Goldwurm, S.
Italy, Milan
Istituti Clinici Di Perfezionamento
Litvan, Irene
Unknown Affiliation
Nicholson, Garth A.
Australia, Sydney
Concord Repatriation General Hospital
Nance, Martha A.
United States, Minneapolis
Struthers Parkinson's Center
Pramstaller, Peter P.
Italy, Bolzano
Regional Hospital of Bolzano
PEZZOLI, GIANNI
Italy, Milan
Istituti Clinici Di Perfezionamento
Itin, Ilia
United States, Cleveland
Cleveland Clinic Foundation
Cambi, Franca
United States, Lexington
University of Kentucky College of Medicine
Kay, Denise M.
United States, Albany
Wadsworth Center for Laboratories and Research
Griffith, Alida F.
United States, Kirtland
Evergreen Hospital Medical Center
Zabetian, Cyrus P.
United States, Seattle
Va Puget Sound Health Care System
Clark, Lorraine N.
United States, New York
Columbia University Irving Medical Center
Louis, Elan Daniel
United States, New York
Columbia University Irving Medical Center
United States, New York
Gertrude H. Sergievsky Center
Côté, Lucien J.
United States, New York
Columbia University Irving Medical Center
United States, New York
Gertrude H. Sergievsky Center
Waters, Cheryl H.
United States, New York
Columbia University Irving Medical Center
Ford, Blair
United States, New York
Columbia University Irving Medical Center
Fahn, Stanley
United States, New York
Columbia University Irving Medical Center
Vance, Jeffery M.
United States, Coral Gables
University of Miami
Beecham, Gary W.
United States, Coral Gables
University of Miami
Pericak-Vance, Margaret Ann
United States, Coral Gables
University of Miami
Haines, Jonathan L.
United States, Cleveland
Case Western Reserve University
DeStefano, Anita L.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
United States, Boston
School of Public Health
United States, Framingham
Framingham Heart Study
Seshadri, Sudha S.
United States, Framingham
Framingham Heart Study
Choi, Seunghoan
United States, Framingham
Framingham Heart Study
Psaty, Bruce M.
United States, Seattle
University of Washington
United States, Washington, D.c.
United States Department of Health and Human Services
United States, Seattle
Group Health Research Institute
Longstreth, William T.
United States, Seattle
University of Washington
van Duijn, Cornelia M.
Netherlands, Rotterdam
Erasmus Mc
Singleton, Andrew B.
United States, Bethesda
National Institute on Aging Nia
Cookson, Mark Robert
United States, Bethesda
National Institute on Aging Nia
Gibbs, Jesse Raphael
United States, Bethesda
National Institute on Aging Nia
United Kingdom, London
Ucl Queen Square Institute of Neurology
Hernandez, Dena G.
United States, Bethesda
National Institute on Aging Nia
United Kingdom, London
Ucl Queen Square Institute of Neurology
Nalls, Michael A.
United States, Bethesda
National Institute on Aging Nia
Zonderman, Alan B.
United States, Bethesda
National Institutes of Health Nih
Ferrucci, Luigi G.
United States, Bethesda
National Institute on Aging Nia
Longo, Dan L.
United States, Bethesda
National Institutes of Health Nih
Traynor, Bryan J.
United States, Bethesda
National Institute on Aging Nia
Troncoso, Juan Carlos
United States, Baltimore
Johns Hopkins University
Weale, Michael E.
United Kingdom, London
King's College London
Ramasamy, Adaikalavan
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
King's College London
Dardiotis, Efthymios
Greece, Volos
University of Thessaly
Spanaki, Cleanthe
Greece, Rethymnon
University of Crete
Plaitakis, Andreas
Greece, Rethymnon
University of Crete
Bozi, Maria
Greece, Athens
Hygeia Hospital
Greece, Athens
National and Kapodistrian University of Athens
Stefanis, Leonidas
Greece, Athens
National and Kapodistrian University of Athens
Greece, Athens
Academy of Athens
Vassilatis, Demetrios K.
Greece, Athens
Academy of Athens
Koutsis, Georgios
Greece, Athens
Eginition Hospital
Hadjigeorgiou, Georgios M.
Greece, Volos
University of Thessaly
Parkkinen, Laura
United Kingdom, Oxford
University of Oxford
Ansorge, Olaf
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
John Radcliffe Hospital
Statistics
Citations: 1,378
Authors: 200
Affiliations: 152
Identifiers
Doi:
10.1038/ng.3043
ISSN:
10614036
Research Areas
Genetics And Genomics
Study Design
Case-Control Study
Study Approach
Systematic review